Overview

The main focus of the ZAUM group Environment is the interplay between environmental exposure and allergy tolerance. Research covers the climatic and anthropogenic changes of the environment and addresses the question, why allergy prevalence is increasing. The group aims on estimating risks, to develop forecasting methods, to enable primary prevention and discover mechanisms that are important for the prevention and the treatment of allergies. The estimation of risks should lead to preventive steps in order to avoid the spreading of allergens and allergies, like novel allergies against the invading neophyte Ambrosia artimisiifolia.
 
Priorities

  1. The group “Environment” mainly investigates how environmental and climatic changes modify the allergenicity of airborne pollen (www.CK-CARE.ch; www.hialine.eu). Here we measure the daily ambient exposure of endotoxin, molds, pollen and airborne allergens at two locations (Munich and Davos, Switzerland) in 2 fractions of ambient air: PM>10 and 10µm>PM>2.5µm (collaboration with Prof. Dr. C. Traidl-Hoffmann, UNIKA-T, Augsburg)
  2. Another research topic is the influence of environmental pollution on allergies due to waste products of combustion (fine dust and the organic phase connected to them, e. g. carbon black; www.HICE-vi.eu).
  3. A third priority is the monitoring and prediction of pollen flight in Bavaria using a network of online pollen monitors (project ePIN – electronic Pollen Information Network for Bavaria) that was selected by the Bavarian Cabinet as an example project for „Bavaria online“ in 2015.
  4. Allergen sources vary in their allergenic potential depending on environmental and genetic factors. This is true for pollen (see below), but also cats. We are developing a method to predict the allergenicity of cats.
  5. Mechanisms of allergenicity. The Aryl Hydrocarbon receptor (AHR) is one of many central keys in the mammalian immune system. This receptor is activated by environmental pollutants present in combustion products (see above and below) plus by sunlight. We focus on the downstream factors controlled by the human immune system and their role in allergic disease.

 

Research projects


The group discovered that pollen display an at least 10-fold biological variability when releasing allergens. This result is important for patients with allergies, because symptoms depend on the quantity of the allergen. For the comprehensive investigation of this important correlation a pan-European project was initiated in order to classify the most common released allergens across Europe. The aim, in the interest of the patient, is to develop an early warning system (www.HIALINE.EU). This project was coordinated by Prof. Buters and was sponsored by the European Union.

 

 

The investigation of anthropogenic agents of combustion (i.e. diesel engine, wood combustion particles) and their influence on the human immune system is a further project, which is of special relevance for our urbanized environment (www.HICE-vi.eu). Because combustion cannot always be modeled in our laboratories (like ship engines), a mobile laboratory was constructed that enables on the spot analysis.
Combustion products occur mainly outdoors, indoor particles are important as well because most individuals stay indoors more than 90% of their time. Our observation is that the fine dust contamination indoor is much higher than outdoor, and that indoor particles (PM10) are toxicologically at least if not more active than outdoor air particles. We analyze the toxicological impact of airborne particles from elementary schools (PAMINA, Particulate Matter in Indoor Ambient Air). The risk deriving from these dusts is presently higher than from outdoor particles.

Our organism is not defenseless against environmental agents, but metabolizes these chemical agents. Ironically, agents can be generated, which are sometimes more toxic than the mother agent. The group integrates the role of metabolizing enzymes in these processes and allows identification of susceptible individuals.

Technology

  1. We possess a mobile S2-Labortory enabling us to do cell culture at any place needed.
  2. Exposure of fresh environmental pollutants to human (primary) cells at the air liquid interface (also in the mobile laboratory).
  3. Air sampling techniques of particulate matter and analytical procedures: PM>10µm, 10µm>PM>2.5µm, 2.5µm>PM>0.1µm with high (800l/min) and low volume (10-30 l/min) samplers on polyurethane foam and Teflon filters in urban, mountainous and indoor environments.
  4. Electron Microscopy and Elemental analysis of individual particles with EDX (Electron Diffraction X-ray) using scanning electron microscopy, and general electron microscopic imaging. Daily spores and pollen quantification in outdoor air (also online!), and daily major allergen determination Bet v 1, Phl p 5, Ole e 1, Amb a 1 and endotoxin (rFC-Method). Automated pollen counting, and Air-Liquid cell exposure.

Molecular biology

cDNA-directed expression system of human and rodent cytochromes P450 CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2D6, 2E1, 3A4, 3A4. RT-PCR of glutathione-S-transferases GST M1, T1, and P1, micro-array genome-wideTranscriptome analysis (Agilent Inc.), Taqman low density real-time PCR-arrays, recombinant gene expression in human primary T-cells („gain of function“).

Cellular systems

Primary human lung cells, primary dermal human mast cells, Fc?R1-humanized Rat Basophils (used as biomarker of outdoor allergens), Human Adenovirus 12-SV40 immortalized lung epithelial cells BEAS-2B, FcER1-Humanized rat basophil cell line (Bioassay for allergens), FcER1-positive murine mast cells, human mast cell line LAD2 and many others.

Toxicological evaluation

Cytotoxicity (endpoints: ATP depletion, mitochondrial instability etc.); Cytotoxicity after metabolic activation by cytochrome P450 CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2D6, 2E1, 3A4, 3A5; Lung toxicity evaluation after Air-Liquid exposure of human bronchial epithelial cells.

 

 

Contact

Prof. Dr. rer. pharm. Jeroen Buters

Zentrum Allergie und Umwelt (ZAUM)
Technische Universität und Helmholtz Zentrum München

Biedersteiner Str. 29
80802 München

Phone: +49 89 4140-3487
E-mail: